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排序方式: 共有1319条查询结果,搜索用时 11 毫秒
11.
Peter K. Windsor Stephen P. Plassmeyer Dominic S. Mattock Jonathan C. Bradfield Erika Y. Choi Bill R. Miller III Byung Hee Han 《International journal of molecular sciences》2021,22(6)
Deposition of amyloid β (Aβ) fibrils in the brain is a key pathologic hallmark of Alzheimer’s disease. A class of polyphenolic biflavonoids is known to have anti-amyloidogenic effects by inhibiting aggregation of Aβ and promoting disaggregation of Aβ fibrils. In the present study, we further sought to investigate the structural basis of the Aβ disaggregating activity of biflavonoids and their interactions at the atomic level. A thioflavin T (ThT) fluorescence assay revealed that amentoflavone-type biflavonoids promote disaggregation of Aβ fibrils with varying potency due to specific structural differences. The computational analysis herein provides the first atomistic details for the mechanism of Aβ disaggregation by biflavonoids. Molecular docking analysis showed that biflavonoids preferentially bind to the aromatic-rich, partially ordered N-termini of Aβ fibril via the π–π interactions. Moreover, docking scores correlate well with the ThT EC50 values. Molecular dynamic simulations revealed that biflavonoids decrease the content of β-sheet in Aβ fibril in a structure-dependent manner. Hydrogen bond analysis further supported that the substitution of hydroxyl groups capable of hydrogen bond formation at two positions on the biflavonoid scaffold leads to significantly disaggregation of Aβ fibrils. Taken together, our data indicate that biflavonoids promote disaggregation of Aβ fibrils due to their ability to disrupt the fibril structure, suggesting biflavonoids as a lead class of compounds to develop a therapeutic agent for Alzheimer’s disease. 相似文献
12.
HER2 targeted therapies have significantly improved prognosis of HER2-positive breast and gastric cancer. HER2 overexpression and mutation is the pathogenic driver in non-small cell lung cancer (NSCLC) and colorectal cancer, however, to date, there are no approved HER2-targeted therapies with these indications. Trastuzumab deruxtecan (T-DXd) is a novel HER2-directed antibody drug conjugate showing significant anti-tumor activity in heavily pre-treated HER2-positive breast and gastric cancer patients. Preliminary data have shown promising objective response rates in patients with HER2-positive NSCLC and colorectal cancer. T-DXd has an acceptable safety profile, however with concerns regarding potentially serious treatment-emergent adverse events. In this review we focus on the pharmacologic characteristics and toxicity profile of T-Dxd, and provide an update on the most recent results of clinical trials of T-DXd in solid tumors. The referenced papers were selected through a PubMed search performed on 16 March 2021 with the following searching terms: T-DXd and breast cancer, or gastric cancer, or non-small cell lung cancer (NSCLC), or colorectal cancer. Oral presentation, abstracts, and posters presented at the American Society of Clinical Oncology (ASCO, Alexandria, VA, USA) 2020 and the European Society for Medical Oncology (ESMO, Lugano, Switzerland) 2020 annual meetings were retrieved for data on T-DXd. We also overview ongoing research and data of combination therapies currently under investigation, which will impact on future therapeutic strategies. Clinicaltrials.gov was searched to identify ongoing clinical trials of T-DXd alone or in combination in solid tumors. 相似文献
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14.
Erika Nassar Chris Mulligan Lem Taylor Chad Kerksick Melyn Galbreath Mike Greenwood Richard Kreider Darryn S Willoughby 《Journal of the International Society of Sports Nutrition》2007,4(1):14-13
Melatonin and resistance exercise alone have been shown to increase the levels of growth hormone (GH). The purpose of this
study was to determine the effects of ingestion of a single dose of melatonin and heavy resistance exercise on serum GH, somatostatin
(SST), and other hormones of the GH/insulin-like growth factor 1 (IGF-1) axis. Physically active males (n = 30) and females
(n = 30) were randomly assigned to ingest either a melatonin supplement at 0.5 mg or 5.0 mg, or 1.0 mg of dextrose placebo.
After a baseline blood sample, participants ingested the supplement and underwent blood sampling every 15 min for 60 min,
at which point they underwent a single bout of resistance exercise with the leg press for 7 sets of 7 reps at 85% 1-RM. After
exercise, participants provided additional blood samples every 15 min for a total of 120 min. Serum free GH, SST, IGF-1, IGFBP-1,
and IGFBP-3 were determined with ELISA. Data were evaluated as the peak pre- and post-exercise values subtracted from baseline
and the delta values analyzed with separate three-way ANOVA (p < 0.05). In males, when compared to placebo, 5.0 mg melatonin
caused GH to increase (p = 0.017) and SST to decrease prior to exercise (p = 0.031), whereas both 0.5 and 5.0 mg melatonin
were greater than placebo after exercise (p = 0.045) and less than placebo for SST. No significant differences occurred for
IGF-1; however, males were shown to have higher levels of IGFBP-1 independent of supplementation (p = 0.004). The 5.0 mg melatonin
dose resulted in higher IGFBP-3 in males (p = 0.017). In conclusion, for males 5.0 mg melatonin appears to increase serum
GH while concomitantly lowering SST levels; however, when combined with resistance exercise both melatonin doses positively
impacts GH levels in a manner not entirely dependent on SST. 相似文献
15.
A. Grüneis M.H. Rümmeli C. Kramberger A. Barreiro T. Pichler R. Pfeiffer H. Kuzmany T. Gemming B. Büchner 《Carbon》2006,44(15):3177-3182
We have synthesized double wall carbon nanotubes (DWNTs) with few defects and little amorphous carbon by hot wall chemical vapor deposition (CVD) of alcohol. Catalysts for the DWNT growth were made from cobalt and molybdenum acetates. Scanning electron microscopy, transmission electron microscopy, multi frequency resonance Raman spectroscopy and optical absorption spectroscopy were used for characterization of the product with regard to DWNT yield, the nanotube diameter distribution, defect concentration and amorphous carbon content. Base pressures lower than 1 × 10−5 mbar in the CVD reactor considerably suppress defects in the DWNTs. Optimized growth conditions for DWNT formation are presented. 相似文献
16.
Colin?WilbornEmail author Jacqueline?Beckham Bill?Campbell Travis?Harvey Melyn?Galbreath Paul?La Bounty Erika?Nassar Jennifer?Wismann Richard?Kreider 《Journal of the International Society of Sports Nutrition》2005,2(2):4-31
Obesity and its associated disorders are a growing epidemic across the world. Many genetic, physiological, and behavioral
factors play a role in the etiology of obesity. Diet and exercise are known to play a valuable role in the treatment and prevention
of obesity and associated disorders such as hypertension, heart disease, and diabetes. Therefore, the purpose of this review
is to examine the prevalence, etiology, consequences, and treatment of obesity. 相似文献
17.
Erika Leitel Wolfgang Hübner Karsten P. Thiessen Ju. B. Makari
ev A. G. Akimov 《工业材料与腐蚀》1988,39(1):1-7
Investigation into the passivation mechanism of iron in phosphate electrolytes on surfaces exposed to erosive attack On iron electrodes in neutral phosphate electrolytes by continuous solid particle impingement a reaction layer is formed within the transition potential region under anodic polarization. XPS and AES investigations show that the reaction layer formed under impingement will be replaced by an oxide layer during the transition into the passive state under simultaneous decrease of the layer thickness. The active/passive transition in phosphate electrolytes may be attached to the equilibrium potential of the reaction . According to this thermodynamic interpretation of both the active/passive transition and the passive/active transition, respectively on iron in presence of phosphate ions may be described as the Fe(II)/Fe(III)-redox reaction with two solid phases, the iron(II)-phosphate phase and the iron(III)-oxide phase. The increase of the interfacial dynamic processes at the solid/liquid interface causes in consequence of the solid particle impingement that thermodynamic laws govern the course of reactions. 相似文献
18.
Johanna Nellen Kai Driessen Martin Neuhäußer Erika Ábrahám Benedikt Wolters 《Information Systems Frontiers》2016,18(5):927-952
In this paper we address the safety analysis of chemical plants controlled by programmable logic controllers (PLCs). We consider a specification of the control program of the PLCs, extended with the specification of the dynamic plant behavior. The resulting hybrid models can be transformed to hybrid automata, for which advanced techniques for reachability analysis exist. However, the hybrid automata models are often too large to be analyzed. We propose two counterexample-guided abstraction refinement (CEGAR) approaches to keep the size of the hybrid models moderate. 相似文献
19.
20.
Samkharadze N Kumar A Manfra MJ Pfeiffer LN West KW Csáthy GA 《The Review of scientific instruments》2011,82(5):053902
We fabricated a He-3 immersion cell for transport measurements of semiconductor nanostructures at ultra low temperatures and in strong magnetic fields. We have a new scheme of field-independent thermometry based on quartz tuning fork Helium-3 viscometry which monitors the local temperature of the sample's environment in real time. The operation and measurement circuitry of the quartz viscometer is described in detail. We provide evidence that the temperature of two-dimensional electron gas confined to a GaAs quantum well follows the temperature of the quartz viscometer down to 4 mK. 相似文献